Abstract

BackgroundInfant cardiac surgery with cardiopulmonary bypass results in decreased circulating alkaline phosphatase that is associated with poor postoperative outcomes. Bovine intestinal alkaline phosphatase infusion represents a novel therapy for post-cardiac surgery organ injury. However, the effects of cardiopulmonary bypass and bovine-intestinal alkaline phosphatase infusion on tissue-level alkaline phosphatase activity/expression are unknown.MethodsInfant pigs (n = 20) underwent cardiopulmonary bypass with deep hypothermic circulatory arrest followed by four hours of intensive care. Seven control animals underwent mechanical ventilation only. Cardiopulmonary bypass/deep hypothermic circulatory arrest animals were given escalating doses of bovine intestinal alkaline phosphatase infusion (0-25 U/kg/hr.; n = 5/dose). Kidney, liver, ileum, jejunum, colon, heart and lung were collected for measurement of tissue alkaline phosphatase activity and mRNA.ResultsTissue alkaline phosphatase activity varied significantly across organs with the highest levels found in the kidney and small intestine. Cardiopulmonary bypass with deep hypothermic circulatory arrest resulted in decreased kidney alkaline phosphatase activity and increased lung alkaline phosphatase activity, with no significant changes in the other organs. Alkaline phosphatase mRNA expression was increased in both the lung and the ileum. The highest dose of bovine intestinal alkaline phosphatase resulted in increased kidney and liver tissue alkaline phosphatase activity.ConclusionsChanges in alkaline phosphatase activity after cardiopulmonary bypass with deep hypothermic circulatory arrest and bovine intestinal alkaline phosphatase delivery are tissue specific. Kidneys, lung, and ileal alkaline phosphatase appear most affected by cardiopulmonary bypass with deep hypothermic circulatory arrest and further research is warranted to determine the mechanism and biologic importance of these changes.

Highlights

  • Infant cardiac surgery with cardiopulmonary bypass results in decreased circulating alkaline phosphatase that is associated with poor postoperative outcomes

  • Total Alkaline phosphatases (AP) activity change after cardiopulmonary bypass (CPB)/deep hypothermic circulatory arrest (DHCA) and the effect of bovine intestinal AP (BiAP) supplementation Total AP activity in each organ is shown in Table 1 by intervention group

  • Group 0 = Anesthesia controls (AC); Group 1 = Animals undergoing CBP/DHCA; Group 2 = Animals undergoing CPB/DHCA with low dose BiAP (3 U/kg bolus followed by 1 U/kg/hr. infusion); Group 3 = Animals undergoing CPB/DHCA with medium dose BiAP (15 U/kg bolus followed by 5 U/kg/hr. infusion); Group 4 = Animals undergoing CPB/DHCA with high dose BiAP (75 U/kg bolus followed by 25 U/kg/hr. infusion)

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Summary

Introduction

Infant cardiac surgery with cardiopulmonary bypass results in decreased circulating alkaline phosphatase that is associated with poor postoperative outcomes. Repair frequently involves cardiopulmonary bypass (CPB) with or without additional techniques to maintain a clear operative field such as deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion [3]. These techniques are not benign and can lead to severe postoperative complications such as systemic inflammation and multiple organ injury [4,5,6,7,8,9,10,11]. AP dephosphorylation of extracellular adenine nucleotides results in creation of adenosine, which has multiple beneficial effects including decreased inflammation, decreased platelet aggregation, vasodilation, and decreased ischemia-reperfusion injury [32,33,34,35,36,37]

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